title: Long-term changes in the material properties of brain tissue at the implant-tissue interface.
abstract: OBJECTIVE
  Brain tissue undergoes dramatic molecular and cellular remodeling at the implant-tissue interface that evolves over a period of weeks after implantation. The biomechanical impact of such remodeling on the interface remains unknown. In this study, we aim to assess the changes in the mechanical properties of the brain-electrode interface after chronic implantation of a microelectrode.
  
  
  METHODS
  Microelectrodes were implanted in the rodent cortex at a depth of 1 mm for different durations-1 day (n = 4), 10-14 days (n = 4), 4 weeks (n = 4) and 6-8 weeks (n = 7). After the initial duration of implantation, the microelectrodes were moved an additional 1 mm downward at a constant speed of 10 µm s(-1). Forces experienced by the microelectrode were measured during movement and after termination of movement. The biomechanical properties of the interfacial brain tissue were assessed from measured force-displacement curves using two separate models-a two-parameter Mooney-Rivlin hyperelastic model and a viscoelastic model with a second-order Prony series.
  
  
  RESULTS
  Estimated shear moduli using a second-order viscoelastic model increased from 0.5-2.6 kPa (day 1 of implantation) to 25.7-59.3 kPa (after 4 weeks of implantation) and subsequently decreased to 0.8-7.9 kPa after 6-8 weeks of implantation in 6 of the 7 animals. The estimated elastic modulus increased from 4.1-7.8 kPa on the day of implantation to 24-44.9 kPa after 4 weeks. The elastic modulus was estimated to be 6.8-33.3 kPa in 6 of the 7 animals after 6-8 weeks of implantation. The above estimates suggest that the brain tissue surrounding the microelectrode evolves from a stiff matrix with maximal shear and elastic modulus after 4 weeks of implantation into a composite of two different layers with different mechanical properties-a stiff compact inner layer surrounded by softer brain tissue that is biomechanically similar to brain tissue-during the first week of implantation. Tissue micromotion-induced stresses on the microelectrode constituted 12-55% of the steady-state stresses on the microelectrode on the day of implantation (n = 4), 2-21% of the steady-state stresses after 4 weeks of implantation (n = 4), and 4-10% of the steady-state stresses after 6-8 weeks of implantation (n = 7).
  
  
  CONCLUSIONS
  Understanding biomechanical behavior at the brain-microelectrode interface is necessary for the long-term success of implantable neuroprosthetics and microelectrode arrays. Such quantitative physical characterization of the dynamic changes in the electrode-tissue interface will (a) drive the design and development of more mechanically optimal, chronic brain implants, and (b) lead to new insights into key cellular and molecular events such as neuronal adhesion, migration and function in the immediate vicinity of the brain implant.
authors.affiliation: School of Biological & Health Systems Engineering, Ira A Fulton School of Engineering, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Arati
authors.initials: A
authors.lastname: Sridharan
authors.forename: Subramaniam D
authors.initials: SD
authors.lastname: Rajan
authors.forename: Jit
authors.initials: J
authors.lastname: Muthuswamy
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D004567:Electrodes, Implanted / Q000639:trends*; D008839:Microelectrodes / Q000639:trends; D019736:Prostheses and Implants / Q000639:trends; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D013499:Surface Properties; D013997:Time Factors; D014783:Viscosity